Mouse pituitary thyrotropic tumors have been a useful model for the investigation of TSH and subunit regulation; however, little information has been obtained for the normal or hypothyroid mouse pituitary. Using antibodies against the purified mouse glycoproteins, we have developed RIAs for mouse TSH and its β-subunit which decreased or eliminated the nonparallelism routinely observed using rat assays. TSH, TSHβ, and α-subunit were measured in the plasma and pituitary of euthyroid mice and short term (41 days) and long term (13 months) hypothyroid mice with and without treatment with T₄ (10 μg/100 g BW, ip) for 12 days. Plasma TSH, free TSHβ and free a concentrations increased progressively with prolongation of hypothyroidism, and treatment with T₄ suppressed all three plasma concentrations in both hypothyroid groups.

The pituitary TSHβ concentration rose 4-fold in short term hypothyroid mice (P < 0.001) and 23-fold in long term hypothyroid mice (P < 0.02). In contrast, the pituitary a concentration fell to 55% (P < 0.01) and 20% (P < 0.001) of euthyroid values in short term and long term hypothyroid mice, respectively. The pituitary TSH concentration was unchanged in short term hypothyroid mice and rose 6-fold in long term hypothyroid mice (P < 0.001). Treatment with T₄ suppressed the pituitary TSHβ concentration in all groups (P < 0.02). In contrast, pituitary a was unchanged after T₄ treatment in euthyroid and short term hypothyroid mice, and actually increased 6-fold in long term hypothyroid mice (P < 0.02). Pituitary TSH was suppressed by T₄ in euthyroid and short term hypothyroid mice (P < 0.05) and was unchanged in long term hypothyroid mice. These divergent responses of pituitary α and TSHβ-subunits to thyroid hormone manipulation suggest fundamental differences in their intrapituitary regulation.